Estimation of the Cadmium Nephrotoxicity Threshold from Loss of Glomerular Filtration Rate and Albuminuria

Abstract

Cadmium (Cd) is a pervasive, toxic environmental pollutant that preferentially accumulates in the tubular epithelium of the kidney. Current evidence suggests that the cumulative burden of Cd here leads to the progressive loss of the glomerular filtration rate (GFR). In this study, we have quantified changes in estimated GFR (eGFR) and albumin excretion (Ealb) according to the levels of blood Cd ([Cd]b) and excretion of Cd (ECd) after adjustment for confounders. ECd and Ealb were normalized to creatinine clearance (Ccr) as ECd/Ccr and Ealb/Ccr. Among 482 residents of Cd-polluted and non-polluted regions of Thailand, 8.1% had low eGFR and 16.9% had albuminuria (Ealb/Ccr) × 100 ≥ 20 mg/L filtrate. In the low Cd burden group, (ECd/Ccr) × 100 < 1.44 µg/L filtrate, eGFR did not correlate with ECd/Ccr (β = 0.007) while an inverse association with ECd/Ccr was found in the medium (β = −0.230) and high burden groups (β = −0.349). Prevalence odds ratios (POR) for low eGFR were increased in the medium (POR 8.26) and high Cd burden groups (POR 3.64). Also, eGFR explained a significant proportion of Ealb/Ccr variation among those with middle (η2 0.093) and high [Cd]b tertiles (η2 0.132) but did not with low tertiles (η2 0.001). With an adjustment of eGFR, age and BMI, the POR values for albuminuria were increased in the middle (POR 2.36) and high [Cd]b tertiles (POR 2.74) and those with diabetes (POR 6.02) and hypertension (2.05). These data indicate that (ECd/Ccr) × 100 of 1.44 µg/L filtrate (0.01–0.02 µg/g creatinine) may serve as a Cd threshold level based on which protective exposure guidelines should be formulated.